Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice:: an experimental study

Background: Peroxisome proliferators-activated receptor alpha ( PPAR alpha) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPAR alpha agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. Methods: Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation ( BDL), III = BDL + vehicle ( gum Arabic), IV = BDL + fenofibrate ( 100 mg/ kg/ day). All rats were sacrificed on 7(th) day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase ( AST), alanine aminotransferase ( ALT) and alkaline phosphatase ( ALP), gamma-glutamyl transferase, ( GGT), tumor necrosis factor alpha ( TNF-alpha), interleukin 1 beta ( IL-I beta), and total bile acid ( TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. Results: Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-alpha, IL-I beta levels, and TBA ( P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals ( P < 0.01). PPAR alpha induction improved all histopathologic parameters ( P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy ( P < 0.01). Conclusion: Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.